摘要
背景心脏手术期间阶段性的缺血一再灌注（ischemia-repeffusion，I，R）常伴随短暂性左室（1eftventricular，LV）功能障碍和炎症反应。本研究探讨了I，R情况下丝氨酸蛋白酶抑制剂抑肽酶（potentialdose．dependenteffectsofapmtinin，APRO）影响LV收缩功能和细胞因子释放的可能剂量依赖性效应。方法应用微传感器容量分析法测定基础水平、缺血30分钟，再灌注60分钟时的LV收缩功能指数，左心室最大弹性（maximaldastance，Emax）。小鼠随机分组为：（a）APRO20000激肽释放酶抑制单位（K1U）／kg组（n=11）；（b）APRO4×104KIU／kg组（n=10）；（C）APRO8×104KIU／kg组（n=10）；（d）溶剂组（生理盐水；n=10）。计算的APRO用量反映临床哈默史密斯剂量表用量的半量、1个剂量和2个剂量。采集I／R后的动物血浆测定细胞因子浓度。结果I／R后溶剂组以及APRO4×104KIU／kg组和APRO8×104KIU／kg组动物Emax较基础水平下降超过40％（P〈0．05）。然而，APRO2×104100／kg组Emax回到接近基础水平。I／R后血浆肿瘤坏死因子（tumornecrosisfactor，TNF）升高10倍，但是TNF随着APRO剂量的增加而下降。结论本研究结果证实，低剂量的APRO对LV收缩功能具有保护作用，而较高剂量APRO可抑制耵师释放。这些独创性的研究结果提示，APRO在I／R情况下具有其不同的独立的作用机制。
BACKGROUND： Periods of ischemia-reperfusion （I/R） during cardiac surgery are associated with transient left ventricular （LV） dysfunction and an inflammatory response. In this study, we examined the potential dose-dependent effects of aprotinin （APRO） on LV contractility and cytokine release in the setting of I/R. METHODS： An index of LV contractility, LV maximal elastance （Emax）, was measured at baseline, 30 rain of ischemia, and 60 min of reperfusion by microtransducer volumetry. Mice were randomized as follows： （a） APRO 20, 000 kallikreininhibiting units （KIU） /kg （n = 11 ）; （b） APRO 4 × 104 KIU/kg （n = 10）; （c） APRO 8 × 104 KIU/kg （n = 10）; and （d） vehicle （saline; n = 10）. APRO doses were calculated to reflect half, full, and twice the clinical Hammersmith dosing schedule. After I/R, plasma was collected for cytokine measurements. RESULTS： After I/R, Emax decreased from the baseline value by more than 40% in the vehide group as well as in the APRO 4 × 104 KIU/kg and APRO 8 ×104 KIU/kg groups （P 〈 0.05）. However, Emax returned to near baseline values in the APRO 2 × 104 KIU/kg group. Tumor necrosis factor （TNF） increased 10-fold after I/R, but it was reduced with higher APRO doses. CONCLUSIONS： This study demonstrated that a low dose of APRO provided protective effects on LV contractility, whereas higher doses suppressed TNF release. These unique findings suggest that there are distinct and independent mechanisms of action of APRO in the context of I/R.
出处
《麻醉与镇痛》
2012年第6期9-16,共8页
Anesthesia & Analgesia
